The present invention relates to malignant tumor metastasis inhibitors. More specifically, it relates to malignant tumor metastasis inhibitors containing an active vitamin D or a derivative thereof as an active ingredient.
The cure rate of malignant tumors is more and more increasing by early diagnosis and progress of therapies, but metastases of malignant tumors are often beyond current therapies and pose one of important medical problems. At present, chemotherapies are used to arrest metastases following removal of tumors with unsatisfactory results, so that it would be desirable to develop more effective inhibitors against malignant tumor metastases.
Bone tissues are one of the most favored sites of metastases of malignant tumors, as a report shows that bone metastases occurred in about 30% of all the cancer cases from autopsy. Among malignant tumors, cancers of the lung, breast, prostate or the like are particularly known to be likely to metastasize to bone.
Vitamin D compounds are known to show a wide variety of physiological activities such as calcium metabolism regulation, growth inhibition or differentiation-inducing of tumor cells or the like, and immunoregulation. Vitamin D derivatives having an oxygen atom at the 22-position which are particularly preferred compounds as malignant tumor metastasis inhibitors of the present invention are known to have very few side effects commonly associated with this type of vitamin D compounds which induce hypercalcemia and they have been reported to be effective for psoriasis, secondary hyperparathyroidism or the like (for example, see JP No. 183534A/1988, JP No. 86382/1994, etc.). They are also known to have antitumor effects, but have not been reported yet to show inhibitory effects against metastases of malignant tumors.
It is an object of the present invention to provide a malignant tumor metastasis inhibitors, and particularly a pharmaceutical agents for inhibiting bone metastases of a malignant tumors.
As a result of extensive research of malignant tumor metastasis inhibitors, it has been found that vitamin D derivatives of the general formula (I): 
wherein R1 represents xe2x80x94Oxe2x80x94R2, xe2x80x94Sxe2x80x94R2,xe2x80x94CH2xe2x80x94R2 or xe2x80x94CHxe2x95x90R2 where R2 represents a C1-C10 chain hydrocarbon group which may be substituted by one or more hydroxyl groups, and R3 represents a hydrogen atom or a hydroxyl group are effective as malignant tumor metastasis inhibitors, particularly as inhibitors against bone metastases of malignant tumors, and thus accomplished the present invention.
Therefore, the present invention relates to malignant tumor metastasis inhibitors containing a compound of the general formula (I): 
wherein R1 represents xe2x80x94Oxe2x80x94R2, xe2x80x94Sxe2x80x94R2xe2x80x94CH2xe2x80x94R2 or xe2x80x94CHxe2x95x90R2 where R2 represents a C1-C10 chain hydrocarbon group which may be substituted by one or more hydroxyl groups, and R3 represents a hydrogen atom or a hydroxyl group, as an active ingredient.